Neoadjuvant treatment response in negative nodes is an important prognosticator after esophagectomy.

BACKGROUND: The current American Joint Committee on Cancer Seventh Edition (AJCC7) pathologic staging for esophageal adenocarcinoma (EAC) is derived from data assessing the outcomes of patients having undergone esophagectomy without neoadjuvant treatment and has unclear significance in patients who have received multimodality therapy. Lymph nodes with evidence of neoadjuvant treatment effect without residual cancer cells may be observed and are not traditionally considered in pathologic reports, but may have prognostic significance. METHODS: All patients who underwent esophagectomy after completing neoadjuvant therapy for EAC at our institution between 2006 and 2012 were reviewed. Slides of pathologic specimens were reexamined for locoregional treatment-response nodes lacking viable cancer cells but with evidence of acellular mucin pools, central fibrosis, necrosis, or calcifications suggesting prior tumor involvement. Kaplan-Meier survival functions were estimated, and Cox proportional hazards regression models were used to compare staging models. RESULTS: Ninety patients (82 men) underwent esophagectomy after neoadjuvant therapy for EAC (mean age, 61.8 ± 8.9 years). All patients received preoperative chemotherapy, and 50 patients also underwent preoperative radiotherapy. Median Kaplan-Meier survival was 55.6 months, and 5-year survival was 35% (95% confidence interval, 19% to 62%). A total of 100 treatment-response nodes were found in 38 patients. For patients with limited nodal disease (62 ypN0-N1), the presence of treatment-response nodes was associated with significantly worse survival (p = 0.03) compared with patients lacking such nodes. Adjusting for patient age and AJCC7 pathologic stage showed the presence of treatment-response nodes significantly increased the risk of death (hazard ratio, 2.7; 95% confidence interval, 1.1 to 6.9; p = 0.04). When stage-adjusted survival was modeled, counting treatment-response nodes as positive nodes offered a better model fit than ignoring them. CONCLUSIONS: Treatment-response lymph nodes detected from esophagectomy specimens in patients having undergone neoadjuvant chemotherapy or combined chemoradiation for EAC provide valuable prognostic information, particularly in patients with limited nodal disease. The current practice of considering lymph nodes lacking viable cancer cells, but with evidence of tumor necrosis, as pathologically negative likely results in understaging. Future efforts at revising the staging system for EAC should consider incorporating treatment-response lymph nodes in the analysis.

24-h multichannel intraluminal impedance-pH monitoring may be an inadequate test for detecting gastroesophageal reflux in patients with mixed typical and atypical symptoms.

BACKGROUND: The detection of gastroesophageal reflux (GERD) via pH testing is the key component of the evaluation of patients considered for antireflux surgery. Two common pH testing systems exist, a multichannel, intraluminal impedance-pH monitoring (MII-pH) catheter, and wireless (Bravo(®)) capsule; however, discrepancies between the two systems exist. In patients with atypical symptoms, MII-pH catheter is often used preferentially. We aimed to elucidate the magnitude of this discrepancy and to assess the diagnostic value of MII-pH and the Bravo wireless capsule in a population of patients with mixed respiratory and typical symptoms. METHODS: The study population consisted of 66 patients tested with MII-pH and Bravo pH testing within 90 days between July 2009 and 2013. All patients presented with laryngo-pharyngo-respiratory (LPR) symptoms. Patient demographics, symptomatology, manometric and endoscopic findings, and pH monitoring parameters were analyzed. Patients were divided into four comparison groups: both pH tests positive, MII-pH negative/Bravo positive, MII-pH positive/Bravo negative, and both pH tests negative. RESULTS: Nearly half of the patients (44%) had discordant pH test results. Of these, 90% (26/29) had a negative MII-pH but positive Bravo study. In this group, the difference in the DeMeester score was large, a median of 29.3. These patients had a higher BMI (28.5 vs. 26.1, p = 0.0357), were more likely to complain of heartburn (50 vs. 23%, p = 0.0110), to have a hiatal hernia, (85 vs. 53%, p = 0.0075) and a structurally defective lower esophageal sphincter (LES, 85 vs. 58%, p = 0.0208). CONCLUSIONS: In patients with LPR symptoms, we found a high prevalence of discordant esophageal pH results, most commonly a negative MII-pH catheter and positive Bravo. As these patients exhibited characteristics consistent with GERD (heartburn, defective LES, hiatal hernia), the Bravo results are likely true. A 24-h MII-pH catheter study may be inadequate to diagnose GERD in this patient population.

Eliminating a need for esophagectomy: endoscopic treatment of Barrett esophagus with early esophageal neoplasia.

Over the past several years, endoscopic ablation and resection have become a new standard of care in the management of Barrett esophagus (BE) with high-grade dysplasia (HGD) or intramucosal adenocarcinoma (IMC). Risk factors for failure of endoscopic therapy and the need for subsequent esophagectomy have not been well elucidated. The aims of this study were to determine the efficacy of radiofrequency ablation (RFA) with or without endoscopic mucosal resection (EMR) in the management of BE with HGD or IMC, to discern factors predictive of endoscopic treatment failure, and to assess the effect of endoscopic therapies on esophagectomy volume at our institution. Data were obtained retrospectively for all patients who underwent endoscopic therapies or esophagectomy for a diagnosis of BE with HGD or IMC in our department between January 1, 2004, and December 31, 2012. Complete remission (CR) of BE or HGD or IMC was defined as 2 consecutive biopsy sessions without BE or HGD or IMC and no subsequent recurrence. Recurrence was defined by the return of BE or HGD or IMC after initial remission. Progression was defined as worsening of HGD to IMC or worsening of IMC to submucosal neoplasia or beyond. Overall, 57 patients underwent RFA with or without EMR for BE with HGD (n = 45) or IMC (n = 12) between 2007 and 2012, with a median follow-up duration of 35.4 months (range: 18.5-52.0 months). The 57 patients underwent 181 ablation sessions and more than half (61%) of patients underwent EMR as a component of treatment. There were no major procedural complications or deaths, with only 2 minor complications including 1 symptomatic stricture requiring dilation. Multifocal HGD or IMC was present in 43% (25/57) of patients. CR of IMC was achieved in 100% (12/12) at a median of 6.1 months, CR of dysplasia was achieved in 79% (45/57) at a median of 11.5 months, and CR of BE was achieved in 49% (28/57) at a median of 18.4 months. Following initial remission, 28% of patients (16/57) had recurrence of dysplasia (n = 12) or BE (n = 4). Progression to IMC occurred in 7% (4/57). All patients without CR continue endoscopic treatment. No patient required esophagectomy or developed metastatic disease. Overall, 6 patients died during the follow-up interval, none from esophageal cancer. Factors associated with failure to achieve CR of BE included increasing length of BE (6.0 ± 0.6 vs 4.0 ± 0.6cm, P = 0.03) and shorter duration of follow-up (28.5 ± 3.8 months vs 49.0 ± 5.8 months, P = 0.004). Shorter surveillance duration (17.8 ± 7.6 months vs 63.9 ± 14.4 months, P = 0.009) and shorter follow-up (21.1 ± 6.1 months vs 43.2 ± 4.1 months) were the only significant factors associated with failure to eradicate dysplasia. Our use of esophagectomy as primary therapy for BE with HGD or IMC has diminished since we began using endoscopic therapies in 2007. From a maximum of 16 esophagectomies per year for early Barrett neoplasia in 2006, we performed only 3 esophageal resections for such early disease in 2012, all for IMC, and we have not performed an esophagectomy for HGD since 2008. Although recurrence of BE or dysplasia/IMC was not uncommon, RFA with or without EMR ultimately resulted in CR of IMC in all patients, CR of HGD in the majority (79%), and CR of BE in nearly half (49%). No patient treated endoscopically for HGD or IMC subsequently required esophagectomy. In patients with BE with HGD or IMC, RFA and EMR are safe and highly effective. The use of endoscopic therapies appears justified as the new standard of care in most cases of BE with early esophageal neoplasia.

Gastroesophageal reflux disease, proton-pump inhibitor use and Barrett's esophagus in esophageal adenocarcinoma: Trends revisited.

PURPOSE: Screening for esophageal adenocarcinoma (EAC) has not become policy in part over concerns in identifying the high-risk group. It is often claimed that a significant proportion of patients developing EAC do not report preexisting reflux symptoms or prior treatment for gastroesophageal reflux disease (GERD). As such, our aim was to assess the prevalence of GERD symptoms, proton pump inhibitor (PPI) use and Barrett's esophagus (BE) and their impact on survival in patients undergoing esophagectomy for EAC. METHODS: The study population consisted of 345 consecutive patients who underwent esophagectomy for EAC between 2000 and 2011 at a university-based medical center. Patients with a diagnosis of esophageal squamous cell carcinoma and those who underwent esophagectomy for benign disease were excluded. The prevalence of preoperative GERD symptoms, defined as presence of heartburn, regurgitation or epigastric pain, PPI use (>6 months) and BE, defined by the phrases "Barrett's esophagus," "intestinal epithelium," "specialized epithelium," or "goblet cell metaplasia" in the patients' preoperative clinical notes were retrospectively collected. Overall long-term and stage-specific survival was compared in patients with and without the presence of preoperative GERD symptoms, PPI use, or BE. RESULTS: The majority of patients (64%; 221/345) had preoperative GERD symptoms and a history of PPI use (52%; 179/345). A preoperative diagnosis of BE was present in 34% (118/345) of patients. Kaplan-Meier survival analysis revealed a marked survival advantage in patients undergoing esophagectomy who had preoperative GERD symptoms, PPI use or BE diagnosis (P ≤ .001). The survival advantage remained when stratified for American Joint Committee on Cancer stage in patients with preoperative PPI use (P = .015) but was less pronounced in patients with GERD symptoms or BE (P = .136 and P = .225, respectively). CONCLUSION: These data show that the oft-quoted statistic that the majority of patients with EAC do not report preexisting GERD or PPI use is false. Furthermore, a diagnosis of BE is present in a surprisingly high proportion of patients (34%). There is a distinct survival advantage in patients with preoperative GERD symptoms, PPI use, and BE diagnosis, which may not be simply owing to earlier stage at diagnosis. Screening may affect survival outcomes in more patients with EAC than previously anticipated.

Treatment strategies for esophageal cancer.

The treatment of esophageal cancer has evolved considerably in the past decade and depends largely on the extent of disease at the time of presentation. For disease confined to the esophageal mucosa, endoscopic therapy is replacing esophagectomy as the standard of care. For locoregional disease, neoadjuvant chemoradiation followed by esophagectomy is the best strategy for optimizing long-term survival. In the minority of patents who present with metastatic disease, the prognosis is poor. Palliative therapies available for these patients include chemotherapy, radiation, endoscopic therapies to ameliorate obstruction or bleeding, and surgical intervention to optimize nutritional status or to relieve obstruction.

Gaze direction modulates visual aftereffects in depth and color.

Prior physiological studies indicate that gaze direction modulates the gain of neural responses to visual stimuli. Here, we test gaze modulation in the perceptual domain using color and depth aftereffects. After confirming retinotopy of the effects, we employed a balanced alternating adaptation paradigm (adaptation alternates between opponent stimuli) to demonstrate that opposite color and depth aftereffects can co-develop at the same retinal location for different gaze directions. The results provide strong evidence for (a) gaze modulation of aftereffects, (b) generality of gaze modulation across two visual attributes, and (c) perceptual correlates of the modulation of neural activity by gaze direction.